This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hypothesis A(1). Caregivers, compared to non-caregivers, will experience more symptoms of depression, anxiety, and sleep difficulties (e.g., shorter sleep time, more awakenings, and reduced sleep efficiency). Within caregivers, the greatest affective disturbance and sleep difficulties will be found among the most highly stressed caregivers and those who exhibit maladaptive coping mechanisms (e.g., avoidance, activity restriction, negative appraisals of caregiving). A(2). The indicators of affective arousal and sleep disturbance in A(1) will be associated with increased sympathoadrenal medullary (SAM) tone reflected by higher circulating catecholamines and decreased beta adrenergic receptor density and sensitivity. A mental stressor task will elicit greatest catecholamine response among the most stressed caregivers. A(3). SAM arousal will be associated with increases in basal inflammatory (e.g., IL-6) and procoagulant (e.g., D-dimer) markers that have previously been associated with heightened risk of cardiovascular disease. A mental stressor task will reveal augmented rise in these molecules among the most stressed caregivers. A(4). The markers of SAM arousal noted in A(2) and A(3) will be associated with markers of cardiovascular injury, including disturbed blood pressure regulation, disturbance in endothelial function, and an increase in subclinical atherosclerosis (i.e. increase in carotid intimal medial thickness (CIMT)). A(5) SAM arousal and the hypothesized downstream consequences listed in A(3) and A(4) will be attenuated by positive coping strategies that include mastery and a problem focused approach.